Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia.
CADASIL
Genotype–phenotype correlation
NOTCH3
Slovakia
Journal
Neurogenetics
ISSN: 1364-6753
Titre abrégé: Neurogenetics
Pays: United States
ID NLM: 9709714
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
14
03
2022
accepted:
08
11
2022
pubmed:
20
11
2022
medline:
11
1
2023
entrez:
19
11
2022
Statut:
ppublish
Résumé
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype-genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.
Identifiants
pubmed: 36401683
doi: 10.1007/s10048-022-00704-6
pii: 10.1007/s10048-022-00704-6
doi:
Substances chimiques
Receptor, Notch3
0
NOTCH3 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-16Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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